1. Field of the Invention
This invention relates to novel 4-hydroxyquinoline derivatives which have been found during the course of systematic studies of 2,3-disubstituted-4-hydroxyquinoline derivatives and which have antagonistic action on leukotriene D.sub.4 and also to a process for chemically preparing the same. The novel 2,3-disubstituted-4-hydroxyquinoline derivatives of the invention strongly antagonize leukotriene D.sub.4 which is energized in the body of mammals in an allergic state and has the action of shrinking organs and are thus useful for curing allergic diseases and particularly, asthma.
2. Description of the Prior Art
Several 2,3-disubstituted-4-hydroxyquinolines have been heretofore isolated as metabolites from microorganisms such as Pseudomonas pyocyaneum [Journal of Antibiotics (J. A.) 39, 1160 (1986) and Chemical Pharmaceutical Bulletin 15, 718 (1967)]. However, some of these compounds have the disadvantage that the production efficiency by microorganism fermentation is very low and their invariable supply is difficult in some cases.
Several 2,3-disubstituted-hydroxyquinoline compounds having an unsaturated hydrocarbon chain at the 2 position are known including 2-(1-heptenyl)-4-quinolone [Journal of Biological Chemistry 159, 725 (1945)], 2-(2-heptenyl)-3-methyl-4-quinolone, 2-(3,6-nonadienyl)-4-quinolone [Chemical Pharmaceutical Bulletin 15, 718 (1967)], and 2-(4-heptenyl)-4-quinolone (Phytochemistry 9, 1283 (1970)].
However, no effective process of preparing 2, 3-disubstituted-4-hydroxyquinoline having an alkyl, alkenyl or alkynyl group at the 2 or 3 position has ever been known up to now.
Moreover, it is known that among the 3-substituted-4-hydroxyquinoline derivatives isolated as a metabolite of microorganism, those having a residue of acrylic acid or its ester at the 3 position are antagonistic against leukotriene D.sub.4, but their activity is generally weak (European Patent Publication No. 55068). The 4 quinolone compounds isolated as the metabolite of a microorganism have an alkyl or alkenyl group having 7-9 carbon atoms at the 2 or 3 position.